RT Journal Article
SR Electronic
T1 Absorption and Metabolization of Cytoprotective Epicatechin Thio Conjugates in Rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 2188
OP 2194
DO 10.1124/dmd.110.035279
VO 38
IS 12
A1 Ariadna Selga
A1 María Pilar Vinardell
A1 Raquel Martín-Venegas
A1 Olga Jáuregui
A1 Josefina Casas
A1 Josep Lluís Torres
YR 2010
UL http://dmd.aspetjournals.org/content/38/12/2188.abstract
AB The epicatechin (EC) thio derivatives 4β-(S-cysteinyl)-epicatechin (Cys-EC) and 4β-(S-cysteaminyl)-epicatechin (Cya-EC) are compounds that may provide protection from oxidation via mechanisms involving either the flavonoid moiety or the nonphenolic cysteine or cysteamine part of the molecule. Because the metabolically modified molecules may be the actual active species, we estimated the absorption/metabolization of the thio derivatives through the small intestine in vitro and studied the body distribution of the compounds and their metabolites in rats. The analysis of the samples generated was done using a high-performance liquid chromatograph coupled to a UV detector and a tandem mass spectrometer. We show that Cya-EC follows the same phase II metabolization pattern as EC, whereas Cys-EC is transported with the intact catechol moiety through the small intestine and effectively metabolized systemically. We also found that Cya-EC generates Cys-EC in vivo, which provides evidence for a Cya-EC-mediated cytoprotective effect through cysteamine/cystine exchange with subsequent cysteine transport, ubiquitously throughout the organism.